研究聚合物共混物对负载莫西丁的PLGA微球(MOX-MS)的体外释放/降解和药代动力学的影响。通过将高(75/25,75kDa)和低(50/50,23kDa)分子量的PLGA以不同比例混合,使用O/W乳液溶剂蒸发法制备了四种制剂(F1,F2,F3和F4)。低分子量PLGA的加入并没有改变微球的释放机制,但加快了微球的药物释放,并大大缩短了滞后期。体外降解结果表明,微球的释放由孔隙扩散和溶蚀相结合,特别是自催化在这一过程中发挥了重要作用。此外,还开发了一种加速释放方法,以减少一个月内的药物释放测试时间。药代动力学结果表明,MOX-MS可以释放至少60天,仅有轻微的血药浓度波动。特别是,F3显示最高的AUC和血浆浓度(AUC0-t=596.53ng/mL·d,洞穴(第30天-第60天)=8.84ng/mL,使其成为最佳配方。总的来说,这些结果表明,使用聚合物共混物可以容易地调节疏水性药物从微球中的释放,并显着减少微球的滞后期。
To investigate the effect of polymer blends on the in vitro release/degradation and pharmacokinetics of moxidectin-loaded PLGA microspheres (MOX-MS), four formulations (F1, F2, F3 and F4) were prepared using the O/W emulsion solvent evaporation method by blending high (75/25, 75 kDa) and low (50/50, 23 kDa) molecular weight PLGA with different ratios. The addition of low-molecular-weight PLGA did not change the release mechanism of microspheres, but sped up the drug release of microspheres and drastically shortened the lag phase. The in vitro degradation results show that the release of microspheres consisted of a combination of pore diffusion and erosion, and especially autocatalysis played an important role in this process. Furthermore, an accelerated release method was also developed to reduce the period for drug release testing within one month. The pharmacokinetic results demonstrated that MOX-MS could be released for at least 60 days with only a slight blood drug concentration fluctuation. In particular, F3 displayed the highest AUC and plasma concentration (AUC0-t = 596.53 ng/mL·d, Cave (day 30-day 60) = 8.84 ng/mL), making it the optimal formulation. Overall, these results indicate that using polymer blends could easily adjust hydrophobic drug release from microspheres and notably reduce the lag phase of microspheres.